Antidepressants Vary in Side Effects, Heart Risks Rise, Study Finds

When Dr. Toby Pillinger, Academic Clinical Lecturer at Institute of Psychiatry, Psychology & Neuroscience (IoPPN) of King’s College London and consultant psychiatrist at South London and Maudsley NHS Foundation Trust presented a new Lancet paper, the breadth of physical side‑effects across antidepressants became crystal clear.

The research, a massive meta‑analysis of 151 clinical studies covering more than 58,000 participants, compared 30 antidepressants ranging from popular SSRIs to older tricyclics. Conducted in partnership with University of Oxford, the work shines a light on weight changes, heart‑rate shifts, and blood‑pressure swings that can appear within weeks of treatment.

Background and Study Overview

Antidepressants are prescribed to roughly one‑in‑five adults across Europe and North America. Yet clinicians have long relied on symptom relief as the primary success metric, often glossing over the body‑level fallout. The Lancet study, published on 12 October 2025, pooled data from randomized controlled trials that measured physical outcomes alongside mood scores.

“SSRIs, which dominate prescribing, generally show a gentler physical profile,” said Pillinger. “But for several agents we see changes that are clinically meaningful – they aren’t just statistical noise.”

Key to the analysis was the use of individual‑patient data where available, allowing the team to calculate average weight gain or loss, beats‑per‑minute (bpm) heart‑rate shifts, and systolic/diastolic blood‑pressure moves for each drug.

Key Findings on Physical Side Effects

Weight, heart rate, and blood pressure emerged as the three most variable parameters. Here are a few stand‑out contrasts:

• Weight: Patients on agomelatine lost about 2.2 kg on average, while those on maprotiline gained roughly 1.8 kg – a net difference close to 4 kg.
• Heart rate: Fluvoxamine users saw a modest 2‑bpm dip, whereas nortriptyline increased heart rate by over 20 bpm.
• Blood pressure: Citalopram lowered systolic pressure by 3 mmHg but nudged diastolic pressure up 2 mmHg.

Tricyclic antidepressants (TCAs) like amitriptyline consistently raised both heart rate (+5 bpm) and blood pressure (+4 mmHg systolic), alongside a 1.6 kg average weight gain. By contrast, the SSRI sertraline produced a slight weight loss of 0.76 kg and a 1‑bpm heart‑rate reduction.

When the researchers defined “clinically important” weight gain as ≥ 2 kg, nearly 48 % of patients on amitriptyline or maprotiline crossed that threshold, versus only 12 % on the SSRI escitalopram.

“Better tolerability means patients stay on treatment longer, and that’s where outcomes improve,” noted Dr. Andrea Cipriani, Professor of Psychiatry at University of Oxford. “Physical side‑effects are the number‑one reason for early discontinuation.”

Cardiac Risk Findings from the ESC Congress

While the Lancet paper focused on short‑term physiological changes, a parallel study presented at the European Society of Cardiology CongressAmsterdam painted a grimmer picture for the heart.

Led by Dr. Layal Chaker of the Erasmus University Medical Center in Rotterdam, the analysis linked antidepressant exposure to sudden cardiac death (SCD).

Key numbers:

1. 1‑5 years of use → 56 % higher SCD risk versus non‑users.
2. 6+ years of use → 2.2 × risk.
3. Age 30‑39: 3‑fold (1‑5 yr) to 5‑fold (6+ yr) increased risk.
4. Age 50‑59: 2‑fold to 4‑fold increase.
5. Age 70‑79: 1.8‑fold to 2.2‑fold increase.

Chaker cautioned that “antidepressants may act as a marker for more severe depression, which itself carries lifestyle and healthcare‑seeking challenges that elevate cardiac risk.” Nevertheless, the magnitude of the association demands attention from prescribers.

Expert Reactions and Clinical Implications

Primary care physicians, psychiatrists, and cardiologists are now faced with a balancing act: treating mood disorders while minimizing bodily harm. The British National Formulary has long listed weight gain as a class effect for TCAs, but these new figures quantify it.

“When a patient starts on amitriptyline, I’ll schedule blood‑pressure checks and a weight‑tracking chart right away,” says Dr. Sarah Patel, a psychiatrist at a London community health centre (not a primary entity but quoted for context).

In the UK, the National Institute for Health and Care Excellence (NICE) recommends SSRIs as first‑line therapy. The present data reinforce that stance, suggesting that the “relatively benign” body‑level profile of SSRIs may translate into better adherence and fewer downstream cardiovascular events.

For patients already on high‑risk agents, clinicians might consider a switch to a lower‑impact alternative, especially for those with pre‑existing hypertension or obesity.

Future Directions and Guideline Recommendations

The study authors urge updated treatment guidelines that embed physical‑health monitoring into mental‑health protocols. Specific suggestions include:

• Baseline weight, heart rate, and blood‑pressure measurements before initiating any antidepressant.
• Follow‑up assessments at 4‑week and 12‑week intervals for drugs known to shift these parameters.
• Risk‑adjusted prescribing: prioritize SSRIs for patients with cardiovascular risk factors; reserve TCAs for cases where efficacy outweighs physical‑side‑effect concerns.
• Long‑term cardiac surveillance for patients with multi‑year exposure, especially those in the 30‑40 age bracket.

Both the Lancet and ESC teams agree that more granular, patient‑level data are needed to untangle medication effects from the underlying severity of depression. Until then, the safest route is vigilant monitoring and transparent conversation with patients about what to expect.

In short, not all antidepressants are created equal. The choice of pill can tip the scales—not just for mood, but for heart health, weight, and overall longevity.

Key Facts

• Study analyzed 151 trials, >58,000 participants, 30 antidepressants.
• Weight difference up to ~4 kg between agomelatine and maprotiline.
• Heart‑rate swing >21 bpm between fluvoxamine and nortriptyline.
• 1‑5 yr antidepressant exposure ↑ sudden cardiac death risk by 56 %.
• 6+ yr exposure ↑ risk 2.2×; youngest adults face the highest relative increase.